We are designing, preparing, and assaying conformationally constrained inhibitors of carnitine acetyltransferase (CAT), carnitine octanoyltransferase (COT), and carnitine palmitoyltransferase (CPT). The primary aim is to identify the topographical arrangement of the key recognition sites on these enzymes by comparing inhibition constants (K- i's) of a series of cyclic analogues. Our long-range goal is to elucidate the structure of the molecular interactions between carnitine and the active site in these enzymes. Identifying these molecular interactions will lead to a better understanding of the physiological chemistry and, more specifically, of the regulation of the enzymes. Beyond the academic interest, these compounds have commercial value. Hemiacylcarnitiniums and morpholiniums show strong binding to carnitine acyltransferases. These inhibitors mimic the putative reaction intermediate in the acyl transfer from carnitine to Coenzyme A. These compounds also mimic carnitine and acylcamitines. They might compete with these natural substrates for other carnitine and acylcarnitine receptors in cells. As such, our compounds have potential for pharmaceutical value in many areas -- hypoglycemic agents, protectors in myocardial ischemia, spermicides, etc. Hemicholinium lipids inhibit protein kinase C and cell- cell aggregation. These compounds inactivate sperm and HIV. Modifications in the design will lead to more selective spermicides and anti-HIV agents. Every eukaryotic cell contains carnitine. Energy production in the cell from fatty acid metabolism depends on carnitine. As carnitine is not synthesized in every cell, proteins transport it across the plasma membrane. More recently, researchers have found a carnitine receptor and a carnitine palmitoyltransferase on erythrocytes, which are cells that lack mitochondria. Our compounds should bind to both of these proteins.